COMPOSITIONS AND METHODS FOR THE TREATMENT OF BRAIN CANCERS
Described herein is an isolated viral particle having a genome that includes open reading frames that encode: Maraba proteins N, P, and L, or variants thereof; as well as Maraba protein M or protein delta 51M, or variants thereof; and a Bahia Grande G protein, a LCMV G protein, or an Ebola G protein. Maraba protein N may have a sequence which includes SEQ ID NO: 1. Maraba protein P may have a sequence which includes SEQ ID NO: 2. Maraba protein L may have a sequence which includes SEQ ID NO: 3. Maraba proteins M and delta 1M may have sequence which include SEQ ID NO: 4 and 5, respectively. Bahia Grande G protein may have a sequence which includes SEQ ID NO: 6. LCMV G protein may have a sequence which includes SEQ ID NO: 7. Ebola G protein may have a sequence which includes SEQ ID NO: 8.
1 . An isolated viral particle having a genome comprising open reading frames that encode:
a protein having a sequence comprising SEQ ID NO: 1, or a variant thereof;
a protein having a sequence comprising SEQ ID NO: 2, or a variant thereof;
a protein having a sequence comprising SEQ ID NO: 3, or a variant thereof;
a protein having a sequence comprising SEQ ID NO: 4 or 5, or a variant thereof; and
a protein having a sequence comprising SEQ ID NO: 6, 7 or 8.
2 . The isolated viral particle according to claim 1 wherein the variant of a reference protein is a protein having a sequence which is at least 75%, at least 80%, at least 85%, at least 90%, or at least 95% identical to the sequence of the reference protein, and the variant protein maintains the same biological function as the reference protein.
3 . The isolated viral particle according to claim 1 , wherein the genome comprises an open reading frame that encodes a protein having a sequence comprising SEQ ID NO: 6.
4 . The isolated viral particle according to claim 1 , wherein the genome comprises an open reading frame that encodes a protein having a sequence comprising SEQ ID NO: 7.
5 . The isolated viral particle according to claim 1 , wherein the genome comprises an open reading frame that encodes a protein having a sequence comprising SEQ ID NO: 8.
6 . The isolated viral particle according to claim 1 , wherein the viral genome comprises open reading frames that encode:
a protein having a sequence comprising SEQ ID NO: 1;
a protein having a sequence comprising SEQ ID NO: 2;
a protein having a sequence comprising SEQ ID NO: 3;
a protein having a sequence comprising SEQ ID NO: 5; and
a protein having a sequence comprising SEQ ID NO: 7.
7 . (canceled)
8 . (canceled)
9 . (canceled)
10 . (canceled)
11 . (canceled)
12 . (canceled)
13 . (canceled)
14 . (canceled)
15 . (canceled)
16 . (canceled)
17 . (canceled)
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . (canceled)
22 . (canceled)
23 . (canceled)
24 . (canceled)
25 . (canceled)
26 . (canceled)
27 . (canceled)
28 . (canceled)
29 . (canceled)
30 . (canceled)
31 . (canceled)
32 . (canceled)
33 . A method for treating cancer comprising administering an isolated viral particle according to claim 1 to a patient having cancer.
34 . The method according to claim 33 wherein the cancer is a brain cancer.
35 . The method according to claim 34 wherein the brain cancer is a glioblastoma.
36 . The method according to claim 33 wherein the isolated viral particle is administered to the patient directly.
37 . The method according to claim 36 wherein the isolated viral particle is administered directly to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof.
38 . The method according to claim 37 wherein the isolated viral particle is administered to the patient intrathecally, intravenously, via intracranial injection, or any combination thereof simultaneously or sequentially.
39 . The method according to claim 33 wherein a cell is infected with the isolated viral particle and the infected cell is administered to the patient.
40 . The method according to claim 39 wherein the infected cell is administered directly to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof.
41 . The method according to claim 39 wherein the infected cell is administered to the patient intrathecally, intravenously, via intracranial injection, or any combination thereof simultaneously or sequentially.
42 . (canceled)
43 . (canceled)
44 . (canceled)
45 . (canceled)
46 . (canceled)
47 . (canceled)
48 . (canceled)
49 . A kit for the treatment of cancer in a patient, the kit comprising:
the isolated viral particle according to claim 1 ; and
instructions for administration of the isolated viral particle to the patient.
50 . The kit according to claim 49 , wherein the cancer is a brain cancer.
51 . The kit according to claim 49 , wherein the brain cancer is a glioblastoma.
52 . The kit according to claim 49 wherein the isolated viral particle is formulated for direct delivery to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof.
53 . The kit according to claim 52 wherein the isolated viral particle is formulated for administration via intrathecal injection, intravenous injection, intracranial injection, or any combination thereof simultaneously or sequentially.
54 . The kit according to claim 59 wherein the isolated viral particle is formulated for infection of a cell and the cell is for delivery to the central nervous system, outside the blood/brain barrier, inside the blood/brain barrier, or any combination thereof.
55 . The kit according to claim 54 wherein the cell is for administration via intrathecal injection, intravenous injection, intracranial injection, or any combination thereof simultaneously or sequentially.